Structures of cobalt(III)-pepleomycin and cobalt(III)-deglycopepleomycin (green forms) determined by NMR studies

被引:44
作者
CaceresCortes, J
Sugiyama, H
Ikudome, K
Saito, I
Wang, AHJ
机构
[1] UNIV ILLINOIS,DEPT CELL & STRUCT BIOL,CHEM & LIFE SCI LAB B107,URBANA,IL 61801
[2] KYOTO UNIV,FAC ENGN,DEPT SYNTHET CHEM & BIOL CHEM,KYOTO,JAPAN
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1997年 / 244卷 / 03期
关键词
pepleomycin; deglycosylated pepleomycin; DNA; two-dimensional NMR; solution structure;
D O I
10.1111/j.1432-1033.1997.00818.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pepleomycin (PEP) is a metalloglycopeptide that has stronger anticancer activity and less pulmonary toxicity than bleomycin (BLM). PEP, like BLM, exerts its action by binding to and degrading DNA in the presence of oxygen and certain metals. Obtaining detailed structural information of PEP and PEP-DNA complexes is crucial to understanding its anticancer activity. The structures of two green forms of cobalt-PEP species, HO2--Co(III)-PEP (denoted CoPEP) and deglycosylated HO2--Co(III)-PEP (denoted CodPEP) have been obtained by NOE restrained refinements. Earlier studies of the related HO2--Co(III)-BLM A(2) proposed that two chiral conformers (form A or B) could exist with either the beta-aminoalanine primary amine (A,NH2) or the mannose carbamoyl nitrogen (M,NH2) as the axial ligand. Analysis of our NOESY data shows convincingly that form A is the most probable conformer with the mannose carbamoyl M,NH2 and the beta-aminoalanine primary amine A,NH2 as the axial ligands in CoPEP and CodPEP, respectively. The NOE cross-peaks resulting from the interactions between the N-terminus (i.e., the metal-binding domain) and the C-terminus of CoPEP and CodPEP have similar patterns, suggesting that they both adopt compact structures with the bithiazole group folded back over the N-terminus.
引用
收藏
页码:818 / 828
页数:11
相关论文
共 51 条
[1]   STUDIES OF THE SOLUTION STRUCTURE OF THE BLEOMYCIN-A2 IRON(II) CARBON-MONOXIDE COMPLEX BY MEANS OF 2-DIMENSIONAL NMR-SPECTROSCOPY AND DISTANCE GEOMETRY CALCULATIONS [J].
AKKERMAN, MAJ ;
NEIJMAN, EWJF ;
WIJMENGA, SS ;
HILBERS, CW ;
BERMEL, W .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (21) :7462-7474
[2]   STUDIES OF THE SOLUTION STRUCTURE OF THE BLEOMYCIN-A2 ZINC COMPLEX BY MEANS OF TWO-DIMENSIONAL NMR-SPECTROSCOPY AND DISTANCE GEOMETRY CALCULATIONS [J].
AKKERMAN, MAJ ;
HAASNOOT, CAG ;
HILBERS, CW .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1988, 173 (01) :211-225
[3]   COMPLETE ASSIGNMENT OF THE C-13 NMR-SPECTRA OF BLEOMYCIN-A2 AND ITS ZINC COMPLEX BY MEANS OF TWO-DIMENSIONAL NMR-SPECTROSCOPY [J].
AKKERMAN, MAJ ;
HAASNOOT, CAG ;
PANDIT, UK ;
HILBERS, CW .
MAGNETIC RESONANCE IN CHEMISTRY, 1988, 26 (09) :793-802
[4]   A SIMPLE METHOD FOR THE PURIFICATION AND ISOLATION OF BLEOMYCIN-A2 [J].
BOGER, DL ;
MENEZES, RF ;
YANG, WJ .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1992, 2 (09) :959-962
[5]  
BRUNGER AT, 1993, XPLOR VERSION 3 2
[6]  
BURGER RM, 1980, J BIOL CHEM, V255, P1832
[7]  
CARTER BJ, 1990, J BIOL CHEM, V265, P4193
[8]   SITE-SPECIFIC CLEAVAGE OF RNA BY FE(II).BLEOMYCIN [J].
CARTER, BJ ;
DEVROOM, E ;
LONG, EC ;
VANDERMAREL, GA ;
VANBOOM, JH ;
HECHT, SM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (23) :9373-9377
[9]   COBALT-BLEOMYCINS AND DEOXYRIBONUCLEIC-ACID - SEQUENCE-DEPENDENT INTERACTIONS, ACTION SPECTRUM FOR NICKING, AND INDIFFERENCE TO OXYGEN [J].
CHANG, CH ;
MEARES, CF .
BIOCHEMISTRY, 1984, 23 (10) :2268-2274
[10]   PROTON NUCLEAR MAGNETIC-RESONANCE STUDY OF BLEOMYCIN IN AQUEOUS-SOLUTION - ASSIGNMENT OF RESONANCES [J].
CHEN, DM ;
HAWKINS, BL ;
GLICKSON, JD .
BIOCHEMISTRY, 1977, 16 (12) :2731-2738